Dose finding in a low-dose 21-day combined oral contraceptive containing gestodene.

An open label, non-comparative study was carried out in 22 women over a total of five cycles. After an untreated cycle, oral administration of 20 microg ethinyl estradiol (EE) with 50 microg gestodene (GST) (tablets taken daily for 21 days with a break of 7 days) was commenced, and three treatment cycles were followed by an untreated follow-up control cycle. The ability of this formulation to inhibit ovulation and suppress ovarian activity was assessed by using hormonal parameters and ultrasound. One ovulation occurred during treatment. Luteinized unruptured follicles were observed in three cases in the second treatment cycle and in one case during the third treatment cycle. Follicle-like structures larger than 13 mm associated with a serum estradiol level of more than 30 pg/mL were noted in 19% of the women in the first treatment cycle. The rate of active follicle-like structures was 43% in the second treatment cycle and 28% in the third treatment cycle. The results were compared with previously reported findings of a preparation containing 20 microg EE and 75 microg GST. With regard to ovarian grading and endogenous hormone secretion, considerably more residual ovarian activity, with all parameters examined, was found in the 20 microg EE and 50 microg GST preparation compared to the 20 microg EE and 75 microg GST preparation. It was concluded that the 20 microg EE and 50 microg GST preparation administered for 21 days does not meet the requirements of a combined oral contraceptive with respect to ovulation inhibition.

Effect of 21-day and 24-day oral contraceptive regimens containing gestodene (60 microg) and ethinyl estradiol (15 microg) on ovarian activity.

OBJECTIVE: To compare ovulation inhibition and ovarian activity with 21-day and 24-day regimens of a low-dose combined oral contraceptive (COC) containing 60 microg of gestodene and 15 microg of ethinyl estradiol. DESIGN: Interventional observational study. SETTING: Reproductive medicine unit. PATIENT(S): Fifty-eight healthy volunteers aged 18-35 years. INTERVENTION(S): Ovarian activity was monitored every other day with the use of ultrasound to measure the diameters of follicle-like structures and blood samples to measure serum concentrations of 17beta-E2 and progesterone. Subjects were observed for five cycles: pretreatment and posttreatment control cycles and three cycles in which the COC was administered for either 21 or 24 days of each cycle. MAIN OUTCOME MEASURE(S): Occurrence of ovulation and evidence of ovarian activity. RESULT(S): The study was completed by 27 (90%) of the 30 subjects who received the 24-day regimen and by 24 (79%) of the 28 subjects who received the 21-day regimen. Ovulation was inhibited in all cycles in the 24-day group and in 74 of 75 cycles in the 21-day group. Luteinized unruptured follicles were seen in no cycles with the 24-day regimen and in 6 (8%) of 75 cycles with the 21-day regimen. Mean ovarian follicular development and serum 17beta-E2 and progesterone levels were lower in the 24-day group. CONCLUSION(S): The 24-day regimen is an innovative strategy for maintaining effective ovulation inhibition at ultra-low doses of contraceptive steroids.

Effect of age on the response of the hypothalamo-pituitary-ovarian axis to a combined oral contraceptive.

OBJECTIVE: To examine the effect of age on the response to treatment with a combined oral contraceptive. DESIGN: Prospective, controlled clinical study. SETTING: Reproductive medicine unit in a tertiary care university medical center. PATIENT(S): Twenty-six healthy female volunteers aged 21-45 years. INTERVENTION(S): After a control cycle, all the women were given a combined oral contraceptive containing 20 microg of ethinylestradiol with 75 microg of gestodene for three cycles. The women were examined through the posttreatment cycle. MAIN OUTCOME MEASURE(S): Pituitary and ovarian activity was assessed with ultrasound and measurement of ovarian steroids. RESULT(S): Follicular activity was observed in all treatment cycles, although ovulation was inhibited. Ovarian suppression was maximal in cycle 1. Mean endogenous E2 levels were lower during cycles 2 and 3 in the older group. Serum FSH levels were higher in the control cycle and on day 28 of the treatment cycles in the older group. Most women ovulated during the posttreatment cycle. CONCLUSION(S): Combined oral contraceptives did not inhibit all ovarian activity; maximal suppression was seen in cycle 1. Less follicular activity was observed in cycles 2 and 3 in the older group. Raised FSH levels with age reflect increasing ovarian resistance to follicular development.

UK accident and emergency departments and emergency contraception: what do they think and do?

OBJECTIVES: A postal questionnaire survey was conducted to assess what staff in UK accident and emergency (A&E) departments thought of providing an emergency contraception service, the degree of enthusiasm in and level of provision of the service, and staff attitudes to the introduction or continuation of provision of the service. METHODS: A questionnaire was sent to all 560 departments providing A&E services in the UK. RESULTS: Of the 560 units sent questionnaires, 355 (63.4%) replied. Half the units were located in small county towns, and a quarter in large towns. Requests for emergency contraception were received by 96% of responding units, but only 57% provided treatment. Requests for emergency contraception in 84 of these units ranged between one and 50 per month. The A&E senior house officer (SHO) and the gynaecology SHO and registrar prescribed most of the pills. Nurses were more involved in nurse led or general practitioner (GP) led units. Initial treatment only was given by 77% of providing units while the remainder also discussed subsequent contraception. Follow up was arranged with GPs by 92 units, and with family planning clinics by 66 units. Information packs were available in only 37 providing units. A total of 155 of providing units felt it was worthwhile and 56% of respondents thought emergency contraception should be provided by A&E departments. However, 91 units could identify one or more groups within the hospital who were antagonistic to provision by A&E departments, of which non-A&E medical staff formed the largest group. Over the counter availability of emergency contraception was not supported by 62% of respondents. CONCLUSION: The results show that while the female population appears to see a need for emergency contraception services to be provided in A&E departments, there is some reluctance by UK A&E departments to provide the service. Given the current interest in approaches to reducing unplanned pregnancies, especially in teenagers, provision of emergency contraception by A&E departments requires a pragmatic approach to ensure their cooperation in providing the service when alternative sources of provision are not available.

PIP: Attitudes toward emergency contraception were assessed in a questionnaire mailed in 1995 to the 560 UK departments that provide accident and emergency services. Consultants, general practitioners, and nurses from 355 departments (63.4%), half of which were located in small county towns, replied. Although 338 units (96.3%) reported they had received requests for emergency contraception, only 198 (57.2%) provided such treatment. Initial treatment only was offered by 150 of the providing units (76.9%); only 45 (23%) also discussed subsequent contraception. Follow-up was organized with general practitioners by 92 units and with family planning clinics by 66 units. 155 of the providing units (82.9%) felt emergency contraception was a worthwhile service. Overall, 177 respondents (55.8%)--78.9% of those already providing emergency contraception and 28.1% of nonproviding units--thought this regimen should be available from emergency departments. Among the reasons cited for opposing such a strategy were unprotected sexual intercourse is a social rather than an acute medical problem, lack of adequate time for counseling and follow-up, and sufficient family planning programs in the area to provide this service. 91 units (42.1%) could identify professional groups (primarily other medical staff) within the hospital who would oppose the introduction or continuation of emergency contraceptive services in the emergency room. Finally, 201 respondents (61.7%) did not support over-the-counter availability of emergency contraception. These findings indicate there is a lack of consensus on whether unprotected intercourse constitutes a medical problem requiring emergency treatment and revealed an appreciable degree of reluctance on the part of accident and emergency departments to provide this service.

Human ovarian granulosa cells and follicular fluid indices: the relationship to oocyte maturity and fertilization in vitro.

The study investigates the correlation between oocyte maturity and fertilization and a variety of hormonal parameters in follicular fluid and ovarian granulosa cells. A methodology for purification of granulosa cells from contaminating blood cells is also established. A total of 63 follicular aspirates were collected at oocyte retrieval from 30 women superovulated using the long luteinizing hormone-releasing hormone (LHRH analogue)/human menopausal gonadotrophin regimen. Oestradiol, progesterone, testosterone and human chorionic gonadotrophin (HCG) were quantified in follicular fluid and granulosa cells were immunostained for human chorionic gonadotrophin. Immunopurification of granulosa cells from contaminating blood cells was performed. HCG in follicular fluid was significantly high in follicles yielding immature (grade 3) oocytes (P=0.002); there was no correlation with fertilization. Aspirates from follicles containing mature (grade 1) oocytes and oocytes that subsequently fertilized had significantly more granulosa cells immunobound to HCG (P < 0.001, P=0.02). Moreover, the immunomagnetic purification technique provided >98% pure population of granulosa cells. The data demonstrate that HCG in follicular fluid and on granulosa cells may help to predict oocyte maturity and fertilization. Furthermore, immunomagnetic beads provide a reliable procedure for the purification of ovarian granulosa cells.

Zoonotic and viral infection in fetal loss after 12 weeks.

One hundred and thirty-six women from an urban, rural and farming community were recruited to a study of infectious causes of midtrimester miscarriage (n = 85), stillbirth (n = 32), or termination for developmental (n = 17) or chromosomal (n = 2) abnormalities. No woman had evidence of acute infection with toxoplasma, listeria, leptospira or Chlamydia psittaci (ovine enzootic abortion). One woman had midtrimester miscarriage associated with primary cytomegolovirus infection and five women had evidence of parvovirus B19 infection, although fetal infection was not proven. Zoonoses were not identified as a cause of fetal loss or malformation in this at-risk population, but parvovirus B19 was a significant cause of midtrimester fetal loss.

Modulation of uterine artery resistance to blood flow by the oral contraceptive pill.

The changes in uterine artery resistance to blood flow were studied during a normal ovulatory cycle (control) and during a cycle on the combined oral contraceptive pill in 10 healthy women, aged 18-35 years, using transvaginal color Doppler imaging. Ovulation was monitored using ultrasound and hormonal assays during both cycles. The Pulsatility Index (PI) was used as a measure of uterine artery resistance, on days 8 (midproliferative) and 22 (midluteal) of the control cycle and on days 22 (maximal ovarian suppression) and 28 (minimal ovarian suppression) of the pill cycle. During the pill cycle, the uterine artery resistance decreased from a mean PI = 4.37 (range 2.4-7.95) on day 22 to a mean of 2.79 (1.94-4.99) on day 28, p = 0.006. The uterine artery resistance was significantly higher on day 22 during the pill cycle compared to the same day of the control cycle, p < 0.0001. Anovulatory cycles on the oral contraceptive pill are associated with an increase in uterine artery resistance and a decrease in uterine perfusion, this effect being reversed during the pill-free week.

Three successive pregnancies in a patient with Takayasu's arteritis.

Takayasu's arteritis is a rare non-specific obliterative panarteritis of unknown origin that occurs predominantly in young Asian and Oriental females of childbearing age and has been encountered in the UK. With the exception of a few large series from the Far East, much of the information on Takayasu's arteritis in pregnancy comes from isolated case reports with no long term follow-up after pregnancy. We report a patient with this condition who had three pregnancies during a 4-year follow-up period with no serious complications.

A multicenter European survey of the attitudes to contraception in women at high risk or with established cardiovascular disease.

OBJECTIVES: The survey was designed to study the attitudes of gynecologists from 11 European centers providing guidance in contraception to women at high risk and women with cardiovascular disease. METHODS: Attitudes were registered by means of a standard questionnaire. RESULTS: Most contributors reported that, in women with venous thrombosis (10/11), deep venous thrombosis (10/11), coagulation disorders (11/11) and stroke (8/11), they prefer to prescribe methods other than combined oral contraceptives (COCs). A history of myocardial infarction was considered a relative contraindication and some experts suggested that, in some cases, the use of third-generation COCs may be possible. COCs were not recommended in women with severe cardiovascular disease and in those over 35 years of age with light or moderate cardiovascular disease, heavy smokers (over 20 cigarettes per day), or those presenting with severe hyperlipidemia. CONCLUSION: The pill is not considered appropriate for women with clinically established cardiovascular diseases or in cases where more than two coronary risk factors exist. COCs may safely be given to women with elevated blood pressure as long as it is lower than 160/100 mmHg, in cases of light and moderate cardiovascular disease as long as the patient is less than 35 years of age, in women who are not heavy smokers, in the presence of a light or moderate degree of hyperlipidemia, and in uncomplicated diabetes mellitus provided that there are no additional risk factors. In these cases, third-generation COCs are preferred. The co-operation of the cardiologist is desirable in order to classify cardiovascular disease and for patient follow-up.

Shorter pill-free interval in combined oral contraceptives decreases follicular development.

The objective of the study was to determine the suppressive effect on ovarian activity of 20 micrograms ethinylestradiol plus 75 micrograms gestodene administered for 21 or 23 days. The study was designed as a double-blind, randomized, multicenter trial in 60 women. A pre-treatment cycle, three treatment cycles and a post-treatment period were monitored by ovarian ultrasound and by LH, FSH, 17 beta-estradiol and progesterone measurements every other day. No ovulation and no luteinized, unruptured follicle were observed. Suppression of ovarian activity was more pronounced by the 23-day regimen. 17 beta-Estradiol serum levels during the last six days of a cycle and during the first six days of the next cycle were significantly less (p < 0.05) in the 23-day regimen. The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown in this study. The observed differences in the 17 beta-estradiol levels and follicular development between a 21-day and 23-day preparation combine to suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations.

PIP: The objective of a double-blind randomized multicenter trial enrolling 60 women was to determine the suppressive effect on ovarian activity of 20 mcg ethinyl estradiol plus 75 mcg gestodene administered for 21 or 23 days. The sites were at the Department of Obstetrics and Gynecology, University of Manchester, UK, and the Institute for Sterility Treatment, Vienna, Austria. The 60 women were healthy volunteers 19-35 years old, and they were randomized with 30 subjects each entering the treatment phase for either the 21-day regimen or the 23-day regimen. A pre-treatment cycle, 3 treatment cycles, and a post-treatment period were monitored by ovarian ultrasound and by measurements of luteinizing hormone (LH), follicle stimulating hormone (FSH), 17-beta-estradiol, and progesterone every other day. Two women on the 21-day regimen forgot to take 1 pill each. Side effects were minor including breast tension, vomiting, nausea, acne, and weight loss or weight gain. Withdrawal bleeding commenced in the 23-day group 2 days later than in the 21-day group. The frequency of intracyclic bleeding decreased when progressing from treatment cycle 1 to 3. No ovulation and no luteinized, unruptured follicle were observed. After stopping the medication, spontaneous ovulations were observed in all volunteers in the 23-day regimen. Suppression of ovarian activity was more pronounced in the 23-day regimen. 17-beta-estradiol serum levels during the last 6 days of a cycle and during the first 6 days of the next cycle were significantly less (p 0.05) in the 23-day regimen. The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown. The observed differences in the 17-beta-estradiol levels and follicular development between the 21-day and 23-day preparations suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations.

Short communication: the effect of mode of delivery on contractile function of placental arteries in vitro.

This study was designed to determine the effect of the mode of delivery on the in vitro assessment of placental blood vessel function. Twenty-two subjects with uncomplicated pregnancies, normal antenatal Doppler flow velocity waveforms and normal birth weights were recruited for the study. The 11 subjects who were delivered by elective caesarean section were matched with 11 controls, who had uncomplicated labours and spontaneous vaginal delivery. Two tertiary chorionic plate arteries were dissected free 1 h after delivery and mounted in a myograph. Cumulative concentration response curves were constructed to the thromboxane A2 analogue U46619, prostaglandin F2 alpha and angiotensin II. After a period of 12 h a further two vessels were mounted and a concentration response curve to U46619 was repeated to determine whether a delay of several hours after delivery would have an effect on the responses of these vessels. These placental arteries constrict to U46619, prostaglandin F2 alpha and angiotensin II in a dose-dependent manner. There was no statistical difference in the maximum contractile responses or pD2 values between the different modes of delivery. A delay in dissection of up to 12 h had no effect on the maximum response or pD2 with U46619. Therefore, contractile function of placental arteries is unaffected by mode of delivery or a delay in dissection.

Human chorionic gonadotrophin and steroid concentrations in follicular fluid: the relationship to oocyte maturity and fertilization rates in stimulated and natural in-vitro fertilization cycles.

The study investigates the relationship of follicular fluid steroids and human chorionic gonadotrophin to oocyte maturity and fertilization rates in stimulated and natural cycles. Oestradiol, progesterone, testosterone and human chorionic gonadotrophin were quantified in 129 samples of follicular fluid and the progesterone:oestradiol ratio calculated. Both stimulated cycles (short and long luteinizing hormone-releasing hormone/human menopausal gonadotrophin regimens) and natural cycles were compared. A total of 60 women were studied, 20 in each group. In the natural cycles, testosterone was significantly lower in follicles with intermediate oocytes (P = 0.015). Both oestradiol and testosterone were significantly lower in stimulated cycles compared to natural cycles (P = 0.032 and P = 0.034 respectively). In the ovarian stimulation cycles, the progesterone:oestradiol ratio was significantly higher when oocytes fertilized (P = 0.052). Moreover, in the stimulated cycles, oestradiol and human chorionic gonadotrophin were singnificantly lower in the short protocol compared to the long protocol. The data demonstrate that the hormonal milieu of the follicle is altered in down-regulated stimulated cycles to varying degrees, depending partially on the type of protocol used. Furthermore, the progesterone:oestradiol ratio, rather than individual hormone concentrations, may be a useful predictor of the fertilizing capacity of the oocytes.

Review of the organized support network for infertility patients in licensed units in the UK.

In acknowledging that 'counselling is generally recognized as beneficial', the Human Fertilization and Embryology Authority (HFEA) Code of Practice requires that all infertility units provide counselling facilities to be available for patients. In this study, we intended to evaluate the support and counselling services made available by the licensed units in the UK. A questionnaire consisting of 30 questions was designed and sent to every licensed treatment unit in the UK. The data were coded on a nominal scale and, using a data entry program, loaded onto a computer. Using the Statistical Package for the Social Sciences program, a non-parametric frequency analysis was performed. Associations were examined with cross-tabulations and chi 2 analysis. A total of 62 units (61.4%) responded to the questionnaire, from both the private and National Health Service sectors. Of these, 95% have their own counsellor, most of whom (84%) practised on the premises. One-third of these counsellors had a dual role, mainly as nurses, social workers or in administration; 98.6% were trained in counselling, with only 28% having either the Certificate or Diploma in Counselling. One-third (32.2%) of centres charged for counselling, with only 13 units indicating their charges. The majority of centres (78.8%) do not actively follow-up patients after counselling and one-quarter (25.5%) did not have a specific counselling room. Over two-thirds (68.4%) of centres described their support network as adequate. The results of this survey suggest that, although the requirements of the HFEA Code of Practice are being adhered to reasonably well, overall patient uptake of counselling is low.(ABSTRACT TRUNCATED AT 250 WORDS)